Design and synthesis of C-linked fucosides as inhibitors of E-selectin

Uchiyama, Taketo; Woltering, Thomas J.; Wong, Weichyun; Lin, Chun-Cheng; Kajimoto, Tetsuya; Takebayashi, Maki; Weitz-Schmidt, Gabriel; Asakura, Tetsuo; Noda, Masatoshi; Wong, Chi‐Huey

doi:10.1016/0968-0896(96)00127-7

Cited by 34 publications

(10 citation statements)

References 40 publications

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“…The crude product was purified via flash column chromatography (eluent: hex/EA = 10:1, v/v) to afford 7h (α, colorless oil, 30.0 mg, 65% yield; α/β = 20:1). Spectral data are in accordance with the literature …”

Section: Experimental Sectionsupporting

confidence: 86%

Mild Cu(OTf)₂-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

Stevens

Wen

et al. 2020

J. Org. Chem.

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C-Glycosylation reactions of glycosyl picolinates with allyltrimethylsilane or silyl enol ethers were developed. Picolinate as a chelation-assisted leaving group could be activated by Cu(OTf)2 and avoided the use of harsh Lewis acids. The glycosylations were operated under mild neutral conditions and gave the corresponding C-glycosides in up to 95% yield with moderate to excellent stereoselectivities.

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Section: Experimental Sectionsupporting

confidence: 86%

Mild Cu(OTf)₂-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

Stevens

Wen

et al. 2020

J. Org. Chem.

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“…The alkene isostere 3 was synthesized via an olefin metathesis between allyl β-C-galactopyranosyl 5 [10] and 1-vinylnaphthalene, followed by deacetylation, and the amide 4 was synthesized by acylation of the aminomethyl β-C-galactopyranosyl 6 [11] (Scheme 1). The yields of the amides 4 and 7-11 were apparently low due to the presence of residual inseparable aluminum salts in C-galactosyl 5 resulting from its synthesis by LiAlH 4 reduction of the preceding nitrile, as originally also reported by Coxon and co-workers for similar reactions [11].…”

Section: Resultsmentioning

confidence: 99%

3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-Sites for High-Affinity and High-Selectivity Inhibition of Galectin-3

et al. 2019

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The galectins are a family of galactose-binding proteins playing key roles in inflammatory processes and cancer. However, they are structurally very closely related, and discovery of highly selective inhibitors is challenging. In this work, we report the design of novel inhibitors binding to a subsite unique to galectin-3, which confers both high selectivity and affinity towards galectin-3. Olefin cross metathesis between allyl β-C-galactopyranosyl and 1-vinylnaphthalenes or acylation of aminomethyl β-C-galactopyranosyl with 1-naphthoic acid derivatives gave C-galactopyranosyls carrying 1-naphthamide structural elements that interacted favorably with a galectin-3 unique subsite according to molecular modeling and X-ray structural analysis of two inhibitor-galectin-3 complexes. Affinities were down to sub-µM and selectivities over galectin-1, 2, 4 N-terminal domain, 4 C-terminal domain, 7, 8 N-terminal domain, 9 N-terminal domain, and 9 C-terminal domain were high. These results show that high affinity and selectivity for a single galectin can be achieved by targeting unique subsites, which holds promise for further development of small and selective galectin inhibitors.

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“…As a wide range of amino acids are commercially available, this approach offers great potential for the preparation of glycopeptide libraries. It is also attractive, because several glycopeptides mimicking the oligosaccharide have displayed relatively higher affinities to their receptors, , while oligosaccharides often bind with relatively low affinities. However, while small glycopeptides are an attractive alternative to complex oligosaccharides, glycopeptides containing naturally occurring (O- or N-linked) carbohydrate−amino acid linkages could be anticipated to be poor therapeutics.…”

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confidence: 99%

Novel Type of Rigid C-Linked Glycosylacetylene−Phenylalanine Building Blocks for Combinatorial Synthesis of C-linked Glycopeptides

et al. 1998

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C-linked 3- and 4-(glycosylacetylene)−Fmoc-phenylalanines were synthesized as rigid building blocks for synthesis of libraries of neoglycopeptide templates. Perbenzylated 1,5-galactonolactone, 1,5- gluconolactone, and 1,5-mannonolactone were reacted with cerium TMS−acetylide and the products reduced to the C-glycosylacetylene−TMS derivatives. The gluco and galacto configurations yielded exclusively the β-C-glycoside, whereas the mannonolactone gave a mixture of α-C- and β-C-anomer. The products were subjected to acetolysis and TMS cleavage. The resulting peracetylated glycosylacetylenes were cross-coupled with the (R,S)-N α-acetyl-3- and 4-iodophenylalanine O-methyl esters by Pd(0) catalysis in piperidine to give the eight possible C-linked glycosyl amino acid building blocks 33−40 as diastereomeric pairs. These were O-deacetylated. As an example of further conversion into neoglycopeptide templates the N-acetyl group of the 4-linked galacto-diastereomeric pair 43 was hydrolyzed selectively by acylase 1 and separated from the (R)-stereoisomer. The product was converted to 4-(β-C-galactosylacetylene)(N α-Fmoc-)-l-phenylalanine (52) by reaction with Fmoc−OSu. Acid hydrolysis of galactosyl acetylene phenyl alanine 43 at elevated temperature afforded the conversion of the acetylene to the 1‘-oxo derivative which was also N α-Fmoc protected. The building blocks were used in the glycopeptide synthesis of three neoglycopeptide templates 54, 55, and 56 known to bind to murine MHC class II Ek and to present the glycan for interaction with the T-cell receptor. This template has previously been employed to elicit a carbohydrate specific T-cell response.

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Design and synthesis of C-linked fucosides as inhibitors of E-selectin

Cited by 34 publications

References 40 publications

Mild Cu(OTf)₂-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

Mild Cu(OTf)₂-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-Sites for High-Affinity and High-Selectivity Inhibition of Galectin-3

Novel Type of Rigid C-Linked Glycosylacetylene−Phenylalanine Building Blocks for Combinatorial Synthesis of C-linked Glycopeptides

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Design and synthesis of C-linked fucosides as inhibitors of E-selectin

Cited by 34 publications

References 40 publications

Mild Cu(OTf)2-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

Mild Cu(OTf)2-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-Sites for High-Affinity and High-Selectivity Inhibition of Galectin-3

Novel Type of Rigid C-Linked Glycosylacetylene−Phenylalanine Building Blocks for Combinatorial Synthesis of C-linked Glycopeptides

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Mild Cu(OTf)₂-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group

Mild Cu(OTf)₂-Mediated C-Glycosylation with Chelation-Assisted Picolinate as a Leaving Group